Ross A. Abrams

OBJECTIVE: The authors reviewed the pathology, complications, and outcomes in a consecutive group of 650 patients undergoing pancreaticoduodenectomy in the 1990s. SUMMARY BACKGROUND DATA: Pancreaticoduodenectomy has been used increasingly in recent years to resect a variety of malignant and benign diseases of the pancreas and periampullary region. METHODS: Between January 1990 and July 1996, inclusive, 650 patients underwent pancreaticoduodenal resection at The Johns Hopkins Hospital. Data were recorded prospectively on all patients. All pathology specimens were reviewed and categorized. Statistical analyses were performed using both univariate and multivariate models. RESULTS: The patients had a mean age of 63 +/- 12.8 years, with 54% male and 91% white. The number of resections per year rose from 60 in 1990 to 161 in 1995. Pathologic examination results showed pancreatic cancer (n = 282; 43%), ampullary cancer (n = 70; 11%), distal common bile duct cancer (n = 65; 10%), duodenal cancer (n = 26; 4%), chronic pancreatitis (n = 71; 11%), neuroendocrine tumor (n = 31; 5%), periampullary adenoma (n = 21; 3%), cystadenocarcinoma (n = 14; 2%), cystadenoma (n = 25; 4%), and other (n = 45; 7%). The surgical procedure involved pylorus preservation in 82%, partial pancreatectomy in 95%, and portal or superior mesenteric venous resection in 4%. Pancreatic-enteric reconstruction, when appropriate, was via pancreaticojejunostomy in 71% and pancreaticogastrostomy in 29%. The median intraoperative blood loss was 625 mL, median units of red cells transfused was zero, and the median operative time was 7 hours. During this period, 190 consecutive pancreaticoduodenectomies were performed without a mortality. Nine deaths occurred in-hospital or within 30 days of operation (1.4% operative mortality). The postoperative complication rate was 41%, with the most common complications being early delayed gastric emptying (19%), pancreatic fistula (14%), and wound infection (10%). Twenty-three patients required reoperation in the immediate postoperative period (3.5%), most commonly for bleeding, abscess, or dehiscence. The median postoperative length of stay was 13 days. A multivariate analysis of the 443 patients with periampullary adenocarcinoma indicated that the most powerful independent predictors favoring long-term survival included a pathologic diagnosis of duodenal adenocarcinoma, tumor diameter <3 cm, negative resection margins, absence of lymph node metastases, well-differentiated histology, and no reoperation. CONCLUSIONS: This single institution, high-volume experience indicates that pancreaticoduodenectomy can be performed safely for a variety of malignant and benign disorders of the pancreas and periampullary region. Overall survival is determined largely by the pathology within the resection specimen.

OBJECTIVE: The objective of this article is to introduce a simple method for classifying cholangiocarcinomas and to apply this system to analyze a large number of patients from a single institution. SUMMARY BACKGROUND DATA: For the past 2 decades, most western reports on cholangiocarcinoma have separated intrahepatic from extrahepatic tumors and have subclassified this latter group into proximal, middle, and distal subgroups. However, "middle" lesions are uncommon and are managed most often either with hilar resection or with pancreatoduodenectomy. The spectrum of cholangiocarcinoma, therefore, is best classified into three broad groups: 1) intrahepatic, 2) perihilar, and 3) distal tumors. These categories correlate with anatomic distribution and imply preferred treatment. METHODS: The records of all patients with histologically confirmed cholangiocarcinoma who underwent surgical exploration at The Johns Hopkins Hospital over a 23-year period were reviewed. RESULTS: Of 294 patients with cholangiocarcinoma, 18 (6%) had intrahepatic, 196 (67%) had perihilar, and 80 (27%) had distal tumors. Age, gender, race, and associated diseases were similar among the three groups. Patients with intrahepatic tumors, by definition, were less likely (p < 0.01) to be jaundiced and more likely (p < 0.05) to present with abdominal pain. The resectability rate increased with a more distal location (50% vs. 56% vs. 91%), and resection improved survival at each site. Five-year survival rates for resected intrahepatic, perihilar, and distal tumors were 44%, 11%, and 28%, and median survival rates were 26, 19, and 22 months, respectively. Postoperative radiation therapy did not improve survival. In a multivariate analysis resection (p < 0.001. hazard ratio 2.80), negative microscopic margins (p < 0.01, hazard ratio 1.79), preoperative serum albumin (p < 0.04, hazard ratio 0.82), and postoperative sepsis (p < 0.001, hard ratio 0.27) were the best predictors of outcome. CONCLUSIONS: Cholangiocarcinoma is best classified into three broad categories. Resection remains the primary treatment, whereas postoperative adjuvant radiation has no influence on survival. Therefore, new agents or strategies to deliver adjuvant therapy are needed to improve survival.

OBJECTIVE: To evaluate, in a prospective, randomized single-institution trial, the end points of operative morbidity, operative mortality, and survival in patients undergoing standard versus radical (extended) pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Numerous retrospective reports and a few prospective randomized trials have suggested that the performance of an extended lymphadenectomy in association with a pancreaticoduodenal resection may improve survival for patients with pancreatic and other periampullary adenocarcinomas. METHODS: Between April 1996 and June 2001, 299 patients with periampullary adenocarcinoma were enrolled in a prospective, randomized single-institution trial. After intraoperative verification (by frozen section) of margin-negative resected periampullary adenocarcinoma, patients were randomized to either a standard pancreaticoduodenectomy (removing only the peripancreatic lymph nodes en bloc with the specimen) or a radical (extended) pancreaticoduodenectomy (standard resection plus distal gastrectomy and retroperitoneal lymphadenectomy). All pathology specimens were reviewed, fully categorized, and staged. The postoperative morbidity, mortality, and survival data were analyzed. RESULTS: Of the 299 patients randomized, 5 (1.7%) were subsequently excluded because their final pathology failed to reveal periampullary adenocarcinoma, leaving 294 patients for analysis (146 standard vs. 148 radical). The two groups were statistically similar with regard to age (median 67 years) and gender (54% male). All the patients in the radical group underwent distal gastric resection, while 86% of the patients in the standard group underwent pylorus preservation ( <.0001). The mean operative time in the radical group was 6.4 hours, compared to 5.9 hours in the standard group ( =.002). There were no significant differences between the two groups with respect to intraoperative blood loss, transfusion requirements (median zero units), location of primary tumor (57% pancreatic, 22% ampullary, 17% distal bile duct, 3% duodenal), mean tumor size (2.6 cm), positive lymph node status (74%), or positive margin status on final permanent section (10%). The mean total number of lymph nodes resected was significantly higher in the radical group. Of the 148 patients in the radical group, only 15% (n = 22) had metastatic adenocarcinoma in the resected retroperitoneal lymph nodes, and none had retroperitoneal nodes as the only site of lymph node involvement. One patient in the radical group with negative pancreaticoduodenectomy specimen lymph nodes had a micrometastasis to one perigastric lymph node. There were six perioperative deaths (4%) in the standard group versus three perioperative deaths (2%) in the radical group ( = NS). The overall complication rates were 29% for the standard group versus 43% for the radical group ( =.01), with patients in the radical group having significantly higher rates of early delayed gastric emptying and pancreatic fistula and a significantly longer mean postoperative stay. With a mean patient follow-up of 24 months, there were no significant differences in 1-, 3-, or 5-year and median survival when comparing the standard and radical groups. CONCLUSIONS: Radical (extended) pancreaticoduodenectomy can be performed with similar mortality but some increased morbidity compared to standard pancreaticoduodenectomy. The data to date fail to indicate that a survival benefit is derived from the addition of a distal gastrectomy and retroperitoneal lymphadenectomy to a pylorus-preserving pancreaticoduodenectomy.

CONTEXT: Among patients with locally advanced metastatic pancreatic adenocarcinoma, gemcitabine has been shown to improve outcomes compared with fluorouracil. OBJECTIVE: To determine if the addition of gemcitabine to adjuvant fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for patients with resected pancreatic adenocarcinoma. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled phase 3 trial of patients with complete gross total resection of pancreatic adenocarcinoma and no prior radiation or chemotherapy enrolled between July 1998 and July 2002 with follow-up through August 18, 2006, at 164 US and Canadian institutions. INTERVENTION: Chemotherapy with either fluorouracil (continuous infusion of 250 mg/m2 per day; n = 230) or gemcitabine (30-minute infusion of 1000 mg/m2 once per week; n = 221) for 3 weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy. Chemoradiation with a continuous infusion of fluorouracil (250 mg/m2 per day) was the same for all patients (50.4 Gy). MAIN OUTCOME MEASURES: Survival for all patients and survival for patients with pancreatic head tumors were the primary end points. Secondary end points included toxicity. RESULTS: A total of 451 patients were randomized, eligible, and analyzable. Patients with pancreatic head tumors (n = 388) had a median survival of 20.5 months and a 3-year survival of 31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence interval, 0.65-1.03]; P = .09). The treatment effect was strengthened on multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P = .05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in the gemcitabine group (P < .001) without a difference in febrile neutropenia or infection. There were no differences in the ability to complete chemotherapy or radiation therapy (>85%). CONCLUSIONS: The addition of gemcitabine to adjuvant fluorouracil-based chemoradiation was associated with a survival benefit for patients with resected pancreatic cancer, although this improvement was not statistically significant. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00003216.